Active ingredients: Fluticasone (Fluticasone furoate)
Avamys 27.5 micrograms per spray, nasal spray, suspension
Why is Avamys used? What is it for?
Avamys (fluticasone furoate) belongs to a group of medicines called glucocorticoids.
Avamys works by decreasing the inflammation caused by allergy (rhinitis) and thus reduces the symptoms of allergy. Avamys Nasal Spray is used to treat the symptoms of allergic rhinitis including a stuffy, runny or itchy nose, sneezing, watery eyes, itching. and redness of the eyes, in adults and children from 6 years of age.
Allergy symptoms can occur at well-defined times of the year and can be caused by allergies to grass or tree pollen (hay fever), or they can occur throughout the year and be caused by allergies to animals. , house dust mites or molds to name a few of the most common.
Contraindications When Avamys should not be used
Do not take Avamys:
- If you are allergic to fluticasone furoate or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Avamys
If you have any liver problems, please tell your doctor or pharmacist.
Children and adolescents
Do not use in children under 6 years of age.
Taking Avamys:
- it can cause children to grow slower if taken for a long time. Your doctor will check your child's height regularly and make sure he is taking the lowest effective dose possible.
- it can cause eye diseases such as glaucoma (increased pressure in the eye) or cataracts (clouding of the lens of the eye). Tell your doctor if you have had these diseases in the past or if you notice any changes in your vision while taking Avamys.
Interactions Which drugs or foods may change the effect of Avamys
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
It is especially important to tell your doctor if you are taking or have recently taken any of the following medicines:
- steroids in tablets or steroids for injection
- steroid based creams
- medicines for asthma
- ritonavir, used to treat HIV
- ketoconazole, used to treat fungal infections
Your doctor will check if you should take Avamys with these medicines.
Avamys should not be used simultaneously with other steroid-containing nasal sprays.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Do not take Avamys if you are pregnant or plan to become pregnant, unless your doctor or pharmacist tells you to take it.
Do not take Avamys if you are breastfeeding unless your doctor or pharmacist tells you to take it.
Driving and using machines
Avamys is unlikely to interfere with your ability to drive or use machines.
Avamys contains benzalkonium chloride
In some patients benzalkonium chloride can cause irritation inside the nose. Tell your doctor or pharmacist if you feel discomfort when using the spray.
Dose, Method and Time of Administration How to use Avamys: Posology
Always use this medicine exactly as your doctor or pharmacist has told you. Do not exceed the recommended doses. If in doubt, consult your doctor or pharmacist.
When to use Avamys
- Take it once a day
- Take it every day at the same time
This allows you to control your symptoms throughout the day and night.
How long does it take Avamys to work
Some people will feel the full effectiveness of Avamys a few days after the first use.
However, it is normally effective within 8-24 hours of the first nasal administration.
How much Avamys to use
Adults and children aged 12 and over
- The normal starting dose is 2 sprays into each nostril once a day, every day.
- Once symptoms are under control it is possible to decrease the dose to 1 spray in each nostril, once a day, every day.
Children between the ages of 6 and 11
- The normal starting dose is 1 spray into each nostril once a day.
- If symptoms are particularly severe, your doctor may increase the dose to 2 sprays in each nostril once a day, every day until symptoms are under control. It may therefore be possible to reduce the dose to 1 spray in each nostril, once a day, every day.
How to use the nasal spray
Avamys practically has no taste or smell. It is sprayed into the nose like a fine mist. Be careful not to splash it in your eyes. If this happens, rinse your eyes with water.
STEP BY STEP GUIDE TO USING THE NASAL SPRAY
What does the nasal spray look like
The nasal spray is presented in an amber glass bottle inserted into a plastic device - see figure a. The bottle contains 30, 60 or 120 puffs, depending on the package that is prescribed.
The window on the side of the plastic inhaler allows you to see the amount of medicine remaining in the bottle. You can see the liquid level for a new bottle of 30 or 60 puffs, but not for a new bottle of 120 puffs, since for the latter the liquid level is above the window.
The six things you need to know about using the nasal spray
- Avamys comes in an amber glass bottle. If you need to check how much medicine is left in the bottle, hold the nasal spray upright against the light. This way you will be able to see the drug level through the window.
- When using the nasal spray for the first time, it should be shaken vigorously for about 10 seconds, with the lid in place. This is important as Avamys is a thick suspension that becomes liquid when shaken well - see figure b. The medicine will spray only when it becomes liquid
- The release button must be firmly pressed down to release the mist through the nozzle
- If you have difficulty pressing the release button with your thumb, you can use both hands
- Always keep the lid in place on the nasal spray when you are not using the medicine. The lid keeps dust out, seals by pressure and prevents the spout from clogging. When the lid is in place, the release button cannot be accidentally pressed.
- Do not use a pin or pointed object to clean the nozzle. This would block the nasal spray.
Preparing the nasal spray for use
The nasal spray must be prepared:
- before its first use
- if the lid has been left in place for 5 days or the intranasal device has not been used for 30 days or more
Preparing the nasal spray ensures that the full dose of medicine is administered. Follow the steps below:
- Shake the nasal spray vigorously with the lid in place for about 10 seconds
- Remove the cover by firmly squeezing the sides of the cover with your thumb and forefinger
- Hold the nasal spray upright, then tilt it and point the nozzle away from you.
- Firmly press the button fully. Repeat the operation for at least 6 times until a thin mist is observed in the air
The nasal spray is now ready for use.
Using the nasal spray
- Shake the nasal spray vigorously.
- 2 Remove the cover.
- 3 Blow your nose to clean the nostrils, then tilt your head forward a little.
- 4 Place the nozzle in one of the nostrils. The nozzle should be positioned inside the nostril towards the outside of the nose, away from the central septum. This promotes the release of the medicine in the right part of the nose.
- Firmly press the button firmly as you inhale through your nose
- Pull out the nozzle and exhale through your mouth.
- If the prescribed dosage is 2 sprays in each nostril, repeat steps 4 to 6.
- Repeat steps 4 to 7 to treat the other nostril.
- Put the lid back on the nasal spray.
Cleaning the nasal spray
After each use:
- Clean the spout and the inside of the lid with a clean, dry tissue
- Do not use water to clean the nasal spray.
- Never use a pin or pointed object on the spout.
- 4 Always put the lid back on the spray after use.
If the nasal spray doesn't seem to work:
- Check if there is any medicine left. Look at the drug level through the window. If the level of the medicine is very low, there may not be enough left for the nasal spray to work.
- Check if the nasal spray has been damaged.
- If you think the nozzle may be blocked, do not use a pin or any sharp object to clean it.
- Try to get it to work again by following the instructions in the "Preparing the Nasal Spray for Use" section.
If the nasal spray still does not work, or if it produces a stream of liquid solution, return the nasal spray to your pharmacist for advice.
Overdose What to do if you have taken too much Avamys
If you take more Avamys than you should
Tell your doctor or pharmacist.
If you forget to take Avamys
If you miss a dose, take it when you remember.
If it is close to taking your next dose, wait until then. Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine or if you have any difficulties using the nasal spray, ask your doctor or pharmacist for advice.
Side Effects What are the side effects of Avamys
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions: contact your doctor immediately
Allergic reactions to Avamys are rare and affect less than 1 in 1000 people. In a small number of people, allergic reactions can develop into a more serious, even life-threatening problem if left untreated. Symptoms include:
- wheezing, coughing or difficulty in breathing
- feeling of sudden weakness or light-headedness (which can lead to collapse or loss of consciousness)
- swelling in the face
- rash or redness.
In many cases, these symptoms will signal less serious side effects. But you should be aware that they can be potentially serious - so if you notice any of these symptoms:
See a doctor as soon as possible.
Very common side effects (may affect more than 1 in 10 people)
- Nosebleed (usually mild), particularly if you take Avamys for more than 6 weeks in a row.
Common side effects (may affect up to 1 in 10 people)
- Nasal ulceration - which can cause irritation or discomfort in the nose. You may also see streaks of blood when you blow your nose.
- Headache
Uncommon side effects (may affect up to 1 in 100 people)
- Pain, burning, irritation or dryness inside the nose.
Not known side effects (frequency cannot be estimated from the available data)
- Growth retardation in children.
- Temporary changes in vision with prolonged use.
Nasal corticosteroids can alter the normal production of steroid hormones in your body, particularly if you use high doses over a long period of time. In children, this side effect can cause them to grow slower than in others.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children
It is best to store Avamys Nasal Spray in an upright position. Always keep the lid on.
Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date refers to the last day of the month. After first use, Avamys Nasal Spray should be used within two months.
Do not store Avamys in the refrigerator or freezer.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Avamys contains
The active ingredient is fluticasone furoate. Each puff delivers 27.5 micrograms of fluticasone furoate.
The other ingredients are anhydrous glucose, dispersible cellulose, polysorbate 80, benzalkonium chloride, disodium edetate, purified water (see section 2).
What Avamys looks like and contents of the pack
The medicine is a nasal spray in the form of a white suspension contained in an amber glass bottle, equipped with a dispensing pump. The bottle is contained in an off-white plastic inhaler with a light blue lid and a side button that activates the spray.
The plastic inhaler has a window to view the contents of the bottle.
Avamys is available in packs of 30, 60 and 120 sprays.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
AVAMYS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each actuation provides 27.5 mcg of fluticasone furoate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Nasal spray, suspension.
White color suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Avamys is indicated in adults, adolescents and children (6 years and older).
Avamys is indicated for the treatment of symptoms of allergic rhinitis.
04.2 Posology and method of administration
Dosage
Adults and adolescents (12 years and over):
The recommended starting dose is two puffs (27.5 mcg of fluticasone furoate for each puff) into each nostril once daily (total daily dose, 110 mcg).
Once adequate symptom control has been achieved, the dose reduced to one puff per nostril (total daily dose 55 mcg) may be effective for maintenance therapy.
The dose should be titrated to the lowest dose at which effective symptom control is maintained.
Children (6 to 11 years old):
The recommended starting dose is one puff (27.5 mcg of fluticasone furoate for each puff) into each nostril once daily (total daily dose, 55 mcg).
Patients who do not respond adequately to a dose of one puff to each nostril once a day (total daily dose, 55 mcg) may use two puffs into each nostril once a day (total daily dose, 110 mcg).
Once adequate symptom control has been achieved, dose reduction to one puff per nostril once daily (total daily dose, 55 mcg) is recommended.
For full therapeutic benefit, regular and scheduled use is recommended. The onset of therapeutic activity is observed from 8 hours after the first administration. However, several days of treatment may be required to get the most benefit. The patient should be informed that symptoms will improve with regular use (see section 5.1). The duration of treatment should be limited to the period corresponding to the duration of exposure to allergens.
Children under the age of 6:
The safety and efficacy of Avamys in children aged less than 6 years have not been established. Currently available data are described in sections 5.1 and 5.2. But no recommendation on a posology can be made.
Elderly patients: No dose adjustment is required in this population (see section 5.2).
Kidney failure
No dose adjustment is required in this population (see section 5.2).
Hepatic insufficiency
No dose adjustment is required in patients with mild to moderate hepatic impairment. No data are available in patients with severe hepatic impairment. Caution should be exercised in dosing in patients with severe hepatic insufficiency as patients with hepatic insufficiency may be more at risk of systemic adverse reactions associated with corticosteroids (see sections 4.4 and 5.2).
Method of administration
Avamys Nasal Spray should only be administered intranasally
Shake the inhaler well before use. To activate the inhaler, hold it upright and press the release button at least 6 times until a fine mist is observed. If the inhaler is left uncovered for 5 days or not used for 30 days or more, repeat the activation process (release about 6 puffs until a thin mist is observed).
After each use, clean the inhaler and replace the lid.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
Systemic effects of corticosteroids
The systemic effects of a corticosteroid, administered nasally, may occur particularly at high doses administered over prolonged periods of time. These effects are less likely to occur than with oral corticosteroid treatment and may vary in individual patients and between different corticosteroid preparations. Possible systemic effects may include Cushing's syndrome, Cushingoid aspect, adrenal suppression, growth retardation in children and adolescents, cataracts, glaucoma and more rarely a range of psychological or behavioral effects including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression (particularly in children).
Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses, consideration should be given to the need for additional systemic corticosteroids during periods of stress or elective surgery. Once daily dosing of fluticasone furoate 110 micrograms has not been associated with suppression of the hypothalamic-pituitary-adrenal axis (HPA) in adult, adolescent or pediatric subjects. However, the dose of intranasal fluticasone furoate should be reduced. as with all intranasal corticosteroids, the total systemic load of corticosteroids should be considered whenever multiple corticosteroid treatments are prescribed simultaneously.
If there is any reason to believe that adrenal function is impaired, particular care should be taken when transferring patients from systemic steroid treatment to fluticasone furoate.
Visual disturbances: Corticosteroids taken by nasal or inhaled route can lead to the development of glaucoma and / or cataracts. Therefore, careful monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and / or cataracts.
Growth delay
Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. A reduction in growth rate was observed in children treated with fluticasone furoate 110 micrograms daily for 1 year (see sections 4.8. And 5.1). Therefore, children should be treated with the lowest effective dose possible for adequate symptom control. (see section 4.2). Regular monitoring of the growth of children who are treated with intranasal corticosteroids for prolonged periods is recommended. If slowed growth is observed, therapy should be re-examined in order to reduce, if possible, the dose of intranasal corticosteroid to the minimum dose that allows effective control of rhinitis symptoms to be maintained. In addition, the need to refer the patient to a pediatrician specialist should be considered (see section 5.1).
Patients on ritonavir therapy
Concomitant administration of ritonavir is not recommended due to the risk of "increased systemic exposure to fluticasone furoate (see section 4.5).
Patients with hepatic insufficiency
The metabolism of Avamys is characterized by an extensive first pass effect, therefore systemic exposure to intranasal fluticasone furoate in patients with severe liver disease is likely to be increased. This may result in an increased frequency of systemic adverse reactions (see sections 4.2 and 5.2) Caution is advised when treating these patients.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction with CYP3A4 inhibitors
Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by cytochrome P450 3A4.
Based on data obtained with another glucocorticoid (fluticasone propionate), which is metabolised by CYP3A4, co-administration with ritonavir is not recommended as there is a risk of increased systemic exposure to fluticasone furoate.
Caution is advised when co-administering fluticasone furoate and potent CYP3A4 inhibitors as an increase in systemic exposure cannot be excluded. In a drug interaction study between intranasal fluticasone furoate and ketoconazole, a potent CYP3A4 inhibitor, was observed more subjects with measurable concentrations of fluticasone furoate in the ketoconazole group (6 of 20 subjects) compared to the placebo group (1 of 20 subjects). This small increase in exposure did not result in a statistically significant difference , in the 24-hour serum cortisol levels between the two groups (see section 4.4).
Enzyme induction and inhibition data suggest that there is no theoretical basis for predicting metabolic interactions between fluticasone furoate and cytochrome P450 mediated metabolism of other compounds at clinically relevant doses administered intranasally. Therefore, no clinical studies have been conducted to evaluate the interactions of fluticasone furoate with other drugs.
04.6 Pregnancy and lactation
Pregnancy
There are insufficient data on the use of fluticasone furoate in pregnant women. In animal studies, glucocorticoids have been shown to cause malformations such as cleft palate and intra-uterine growth retardation. This is likely to be irrelevant to the patient. human since recommended doses for intranasal use result in minimal systemic exposure (see section 5.2). Fluticasone furoate should only be used in pregnancy if the benefits to the mother outweigh the potential risk to the fetus or child.
Feeding time
It is unknown whether intranasally administered fluticasone furoate is excreted in human milk. Administration of fluticasone furoate to breastfeeding women should only be considered when the expected benefit to the mother is greater than any possible risk to the baby.
Fertility
There are no data on fertility in humans.
04.7 Effects on ability to drive and use machines
Avamys has no or negligible influence on the ability to drive and use machines.
04.8 Undesirable effects
Summary of the safety profile The most commonly reported adverse reactions during treatment with fluticasone furoate are epistaxis, nasal ulceration and headache. The most serious side effects are rare cases of hypersensitivity reactions, including anaphylaxis (less than 1 case in 1000 patients).
Tabulated list of adverse reactions In safety and efficacy studies, more than 2700 patients were treated with fluticasone furoate for seasonal and perennial allergic rhinitis. Pediatric exposure to fluticasone in safety and efficacy studies in seasonal and perennial allergic rhinitis included 243 patients 12 to
Data from large clinical trials were used to determine the frequency of adverse reactions.
The following convention has been adopted for the classification of frequencies:
Very common ≥1 / 10; Common ≥1 / 100 -
Description of selected adverse reactions
Epistaxis
* Epistaxis was generally mild to moderate in intensity. In adults and adolescents, the incidence of epistaxis was higher in long-term use (greater than 6 weeks) than in short-term use (up to 6 weeks). at 6 weeks).
Systemic effects
Systemic effects may occur following nasal corticosteroids, particularly when prescribed at high doses for prolonged periods (see section 4.4). Growth retardation has been reported in children receiving nasal corticosteroids.
Pediatric population
Safety in children under the age of 6 has not been well established. Frequency, type and severity of adverse reactions observed in the pediatric population are similar to those in the adult population.
Epistaxis
* In pediatric clinical trials conducted up to 12 weeks duration, the incidence of epistaxis was similar between patients treated with fluticasone furoate and those treated with placebo.
Growth delay
** In a one-year clinical study evaluating growth in pre-pubescent children receiving 110 mcg fluticasone furoate once daily, a mean treatment difference of -0.27 cm per year was observed in growth rate compared to placebo (see Clinical efficacy and safety).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important. It allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Annex V.
04.9 Overdose
In a bioavailability study, intranasal doses of up to 2,640 mcg per day were administered for three days with no adverse systemic reactions observed (see section 5.2).
Acute overdose is unlikely to require any therapy other than observation of the patient.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: nasal preparations, corticosteroids.
ATC code: R01AD12.
Mechanism of action:
Fluticasone furoate is a synthetic trifluorinated corticosteroid which has a very high affinity for the glucocorticoid receptor and has a potent anti-inflammatory action.
Clinical efficacy and safety:
Seasonal allergic rhinitis in adults and adolescents:
Compared to placebo, fluticasone furoate, nasal spray 110 mcg once daily significantly improved nasal symptoms (including runny nose, nasal congestion, sneezing and nasal itching) and ocular symptoms (including itching / burning, tearing, even intense tearing and eye redness). in all 4 studies. The efficacy was maintained throughout the 24 hour period between one administration and the next, with the once daily dosing.
The onset of therapeutic benefit was observed starting 8 hours after the first administration, with further improvements observed for several days thereafter.
Fluticasone furoate nasal spray significantly improved patients' perception of overall response to therapy and disease-related quality of life (Rhinoconjunctivie Quality of Life Questionnaire - RQLQ) in all 4 studies.
Perennial allergic rhinitis in adults and adolescents:
Fluticasone furoate nasal spray 110 mcg once daily significantly improved nasal symptoms as well as patients' perceptions of overall response to therapy compared to placebo in three studies.
In one study, fluticasone furoate nasal spray 110 mcg once daily significantly improved ocular symptoms as well as disease-related quality of life (RQLQ) compared to placebo.
The efficacy was maintained throughout the 24 hour period between doses with the once daily dosing.
In a two-year study to evaluate the ocular safety of fluticasone furoate (110 micrograms once daily intranasally), adults and adolescents with perennial allergic rhinitis were treated with fluticasone furoate (n = 367) or placebo (n = 181). Primary outcomes [time to increase in posterior subcapsular opacity (≥ 0.3 from baseline in Lens Opacities Classification System, version III (LOCS III grade)) and time to increase in intraocular pressure (IOP; ≥ 7 mmHg compared to at baseline)] were not statistically significant between the two groups. Increases in posterior subcapsular opacity (≥ 0.3 from baseline) were more frequent in subjects treated with fluticasone furoate 110 mcg [14 (4%)] compared to placebo [4 (2%)] and were transient in nature for ten subjects in the fluticasone furoate group and two subjects in the placebo group. Increases in IOP (≥ 7 mmHg from baseline) were more frequent in subjects treated with 110 mcg fluticasone furoate : 7 (2%) for fluticasone furoate 110 mcg once daily and 1 (and 104, 95% of subjects in both treatment groups had posterior subcapsular opacity values within ± 0.1 of baseline values for each eye I and, at week 104, ≤ 1% of subjects in both treatment groups had a ≥ 0.3 increase in posterior sub capsular opacity from baseline. At weeks 52 and 104, most subjects (> 95%) had IOP values within ± 5mmHg of baseline. Increases in posterior subcapsular opacity or IOP were not accompanied by adverse events of cataract or glaucoma.
Pediatric population:
Perennial and seasonal allergic rhinitis in children:
Pediatric posology is based on evaluation of efficacy data in the pediatric allergic rhinitis population.
In seasonal allergic rhinitis, fluticasone furoate nasal spray 110 mcg once daily has been shown to be effective. However, no significant differences were observed between fluticasone furoate nasal spray 55 mcg once daily and placebo on any endpoint.
In perennial allergic rhinitis, fluticasone furoate nasal spray 55 mcg once daily for 4 weeks of treatment showed a more consistent efficacy profile than 110 mcg once daily dosing for 4 weeks of treatment. A post-hoc analysis conducted on the same 6- and 12-week study, as well as the 6-week safety study on the hypothalamic-pituitary-adrenal (HPA) axis, supported the efficacy of fluticasone furoate nasal spray 110 micrograms administered. once a day.
A 6-week study investigating the effect of fluticasone furoate nasal spray 110 mcg once daily on adrenal function in children aged 2 to 11 years, demonstrated no significant effect on cortisol profiles. serum over 24 hours, compared to placebo.
A one-year, randomized, double-blind, parallel-group, multicentre, placebo-controlled clinical trial evaluated the effect of fluticasone furoate nasal spray 110 mcg per day on growth rate in 474 pre-pubertal children. (5 to 7.5 years of age for females and 5 to 8.5 years of age for males) with a stadiometer. The mean rate of growth over the 52-week treatment period was slower in patients treated with fluticasone furoate (5.19 cm / year) versus placebo (5.46 cm / year). The mean difference due to treatment was -0.27 cm per year [95% CI -0.48 to -0.06].
Perennial and seasonal allergic rhinitis in children (under 6 years old):
Safety and efficacy studies were conducted for both seasonal and perennial allergic rhinitis in a total of 271 patients 2 to 5 years of age, 176 of whom were exposed to fluticasone fumed.
Safety and efficacy in this age group have not been well established.
05.2 Pharmacokinetic properties
Absorption
Fluticasone furoate undergoes incomplete absorption and extensive first pass metabolism in the liver and intestine, resulting in negligible systemic exposure. Intranasal administration of 110 μg once daily does not normally result in measurable plasma concentrations (pg / ml The absolute bioavailability of intranasally administered fluticasone furoate is 0.50% as less than 1 microgram of fluticasone furoate would be systemically available following administration of 110 micrograms (see section 4.9).
Distribution
The plasma protein binding of fluticasone furoate is greater than 99%. Fluticasone furoate is widely distributed with a steady-state volume of distribution of 608 liters, on average.
Biotransformation
Fluticasone furoate is rapidly cleared from the systemic circulation (total plasma clearance of 58.7 L / h) primarily by hepatic metabolism to the inactive 17β-carboxylic metabolite (GW694301X), by the cytochrome P450 enzyme CYP3A4. by the hydrolysis of the S-fluoromethyl carbothioate function to form the 17β-carboxylic acid metabolite. Education in vivo they did not show cleavage of the furoate portion to form fluticasone.
Elimination
Elimination occurs primarily via the faecal route following oral and intravenous administration, which is indicative of the excretion of fluticasone furoate and its metabolites via the bile. Following intravenous administration the half-life of the elimination phase lasts on average 15.1 hours. Urinary excretion constitutes approximately 1% and 2%, respectively, of the oral and intravenous dose.
Pediatric population
The blood concentration of fluticasone furoate is not quantifiable in the majority of patients (
Senior citizens
Only a small number of elderly patients (≥ 65 years, n = 23/872; 2.6%) provided pharmacokinetic data. There was no higher incidence of patients with quantifiable concentrations of fluticasone furoate among the elderly when compared to the younger patient population.
Kidney failure
Following intranasal administration, fluticasone furoate is not detectable in the urine of healthy volunteers. Less than 1% of the dose-related active substance is excreted in the urine and therefore renal insufficiency is not expected to interfere with the pharmacokinetics of fluticasone furoate.
Hepatic insufficiency
There are no data on intranasal fluticasone in patients with hepatic insufficiency. A study conducted in patients with moderate hepatic insufficiency treated with a single dose of 400 micrograms inhaled orally, resulted in an increase in Cmax (42%) and AUC0-∞ (172%) and a modest decrease ( on average 23%) in cortisol levels of patients compared to healthy subjects. Based on this study, the expected mean exposure of 110 micrograms of intranasal fluticasone furoate in patients with moderate hepatic impairment is not expected to result in cortisol suppression. Therefore, the normal adult dose is not expected to result in cortisol suppression. result in a clinically relevant effect in patients with moderate hepatic insufficiency. There are no data in patients with severe hepatic insufficiency. The exposure to fluticasone furoate in this patient population is likely to be further increased.
05.3 Preclinical safety data
In general toxicology studies, the results were similar to those seen with other corticosteroids and are associated with "excessive pharmacological activity. These findings are likely not relevant to humans, given that recommended nasal doses result in a "minimal systemic exposure. No genotoxic effects of fluticasone were observed on conventional genotoxicity tests. In addition, there were no increases in the incidence of treatment-related tumors in the two-year inhaled studies in mice and rats.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Anhydrous glucose
Dispersible cellulose
Polysorbate 80
Benzalkonium chloride
Disodium edetate
Purified water
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
Validity: 2 months from the first activation.
06.4 Special precautions for storage
Do not refrigerate or freeze.
Store upright. Always keep the cap on.
06.5 Nature of the immediate packaging and contents of the package
14.2 ml in a Type I or Type III amber glass bottle (glass) fitted with a metering spray pump.
The medicine is available in three packs: a bottle of 30, 60 or 120 puffs.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Glaxo Group Ltd
980 Great West Road, Brentford, Middlesex, TW8 9GS
UK
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/07/434/001
038343012
EU / 1/07/434/002
038343024
EU / 1/07/434/003
038343036
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 11 January 2008
Date of most recent renewal: 11 January 2013
10.0 DATE OF REVISION OF THE TEXT
April 2014
